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Modeling mechanisms of interindividual variation in pain modulation by spinal cord stimulation

Award Number: R15AT013512
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Modeling mechanisms of interindividual variation in pain modulation by spinal cord stimulation - Project Summary Approximately 20% of Americans live with chronic pain, the underlying causes of which are often unknown. Spinal cord stimulation (SCS) is a therapy that successfully alleviates chronic pain symptoms in many patients; however, the efficacy of SCS across individuals can vary widely. Recently, clinicians have begun exploring a larger range of SCS frequencies, from more conventional values of 50 Hz (cSCS) up to values as high as 10 kHz (HF-SCS). While some patients receive significant reductions in pain with HF-SCS, others have optimal pain relief with cSCS or other forms of SCS. The mechanisms by which these protocols lead to pain relief in patients with chronic pain remain unclear, especially as concerns the variability across individuals with different chronic pain states. Potential sources of interpatient variability in the efficacy of SCS include variability in the activation of dorsal column (DC) fibers and the corresponding sensory processing of DC input by neural circuitry in the dorsal horn (DH) of the spinal cord. This proposal aims to use biologically-motivated mathematical models at these two scales: a biophysical three-dimensional hybrid field-cable model describing the activity of DC axons due to the electrical potential fields generated from current impulses emitted by an SCS electrode array, and a firing-rate network model of the neural circuitry responsible for sensory processing in the DH. The proposed projects will be in majority be conducted by undergraduate students at Middlebury College, with mentorship by and collaboration with faculty and graduate student trainees in biomedical engineering and applied mathematics at the University of Michigan. This proposal will strengthen the institutional pain research environment at Middlebury College by providing unique opportunities for undergraduate students to not only actively engage in pain multidisciplinary pain research, but also access a cross-organization, vertically-integrated mentorship program. Together, completion of these computational studies will: 1) identify key anatomical features that most robustly contribute to changes in DC axon firing, and 2) predict the mechanism(s) underlying preferential pain-relief responses of projection neurons within dysregulated DH circuitries (i.e., those contributing to chronic pain) to a range of SCS frequencies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $540,427 )
2025	2025	PRESIDENT AND FELLOWS OF MIDDLEBURY COLLEGE	9 OLD CHAPEL RD	MIDDLEBURY	VT	05753	ADDISON	USA	Research and Training in Complementary and Integrative Health	000	1	8/15/2025	NEW	$540,427
														Subtotal = $540,427

Grand Total All Awards = $540,427

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Modeling mechanisms of interindividual variation in pain modulation by spinal cord stimulation

Award Number: R15AT013512

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/18/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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